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dc.contributor.author Szalay, Csaba Imre
dc.contributor.author Erdélyi, Katalin
dc.contributor.author Kökény, Gábor
dc.contributor.author Lajtar E
dc.contributor.author Godo M
dc.contributor.author Revesz C
dc.contributor.author Kaucsár, Tamás
dc.contributor.author Kiss, Norbert
dc.contributor.author Sárközy, Márta
dc.contributor.author Csont, Tamás Bálint
dc.contributor.author Krenács, Tibor
dc.contributor.author Szénási, Gábor
dc.contributor.author Pacher, Pál
dc.contributor.author Hamar, Péter
dc.date.accessioned 2016-02-09T10:38:41Z
dc.date.available 2016-02-09T10:38:41Z
dc.date.issued 2015
dc.identifier 84939204891
dc.identifier.citation pagination=e0127090; journalVolume=10; journalIssueNumber=6; journalTitle=PLOS ONE;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/2325
dc.identifier.uri doi:10.1371/journal.pone.0127090
dc.description.abstract Chronic renal fibrosis is the final common pathway of end stage renal disease caused by glomerular or tubular pathologies. Genetic background has a strong influence on the progression of chronic renal fibrosis. We recently found that Rowett black hooded rats were resistant to renal fibrosis. We aimed to investigate the role of sustained inflammation and oxidative/nitrative stress in renal fibrosis progression using this new model. Our previous data suggested the involvement of podocytes, thus we investigated renal fibrosis initiated by doxorubicin-induced (5 mg/kg) podocyte damage. Doxorubicin induced progressive glomerular sclerosis followed by increasing proteinuria and reduced bodyweight gain in fibrosis-sensitive, Charles Dawley rats during an 8-week long observation period. In comparison, the fibrosis-resistant, Rowett black hooded rats had longer survival, milder proteinuria and reduced tubular damage as assessed by neutrophil gelatinase-associated lipocalin (NGAL) excretion, reduced loss of the slit diaphragm protein, nephrin, less glomerulosclerosis, tubulointerstitial fibrosis and matrix deposition assessed by periodic acid-Schiff, Picro-Sirius-red staining and fibronectin immunostaining. Less fibrosis was associated with reduced profibrotic transforming growth factor-beta, (TGF-beta1) connective tissue growth factor (CTGF), and collagen type I alpha 1 (COL-1a1) mRNA levels. Milder inflammation demonstrated by histology was confirmed by less monocyte chemotactic protein 1 (MCP-1) mRNA. As a consequence of less inflammation, less oxidative and nitrative stress was obvious by less neutrophil cytosolic factor 1 (p47phox) and NADPH oxidase-2 (p91phox) mRNA. Reduced oxidative enzyme expression was accompanied by less lipid peroxidation as demonstrated by 4-hydroxynonenal (HNE) and less protein nitrosylation demonstrated by nitrotyrosine (NT) immunohistochemistry and quantified by Western blot. Our results demonstrate that mediators of fibrosis, inflammation and oxidative/nitrative stress were suppressed in doxorubicin nephropathy in fibrosis-resistant Rowett black hooded rats underlying the importance of these pathomechanisms in the progression of renal fibrosis initiated by glomerular podocyte damage.
dc.relation.ispartof urn:issn:1932-6203
dc.title Oxidative/Nitrative Stress and Inflammation Drive Progression of Doxorubicin-Induced Renal Fibrosis in Rats as Revealed by Comparing a Normal and a Fibrosis-Resistant Rat Strain
dc.type Journal Article
dc.date.updated 2015-11-09T13:04:54Z
dc.language.rfc3066 en
dc.identifier.mtmt 2909364
dc.identifier.wos 000356567500007
dc.identifier.pubmed 26086199
dc.contributor.department SE/AOK/I/I. Sz. Patológiai és Kísérleti Rákkutató Intézet
dc.contributor.department SE/AOK/I/Kórélettani Intézet
dc.contributor.department SE/AOK/I/IISZPI/MTA-SE Molekuláris Onkológia Kutatócsoport
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote Pacher P and Hamar P contributed equally to this work.


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